X-ray crystal structure of TNF ligand family member TL1A at 2.1 Å

Abstract

The TNF family has been one of the most intensively studied protein families in the past two decades and it has rapidly expanded through the era of genomics and bioinformatics. However, the structural basis of the functional and interactional similarities and differences of this family is poorly understood. TL1A is a recently identified TNF family member that has received increasing attention. Here, the crystal structure of human TL1A is reported. TL1A forms a homotrimer with each monomer assuming a jellyroll β-sandwich fold. The CD loop in TL1A is the longest among the TNF ligand members with known structure and the AA′ loop in TL1A is the second longest after that in TRAIL, where part of it is disordered. Both these loops are known to participate in receptor binding in TNFβ/LTα. The AA′ loop may be very different in other TL1A variants if the overall fold is to be preserved.